{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:23:06Z","timestamp":1760059386800,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut de Recherche En Sant\u00e9 Publique (IRESP)","award":["A21030DS"],"award-info":[{"award-number":["A21030DS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: D-lysergic acid diethylamide (D-LSD) is under investigation as a potential therapeutic strategy for alcohol use disorder (AUD). However, the extreme light sensitivity of D-LSD presents a significant challenge in developing suitable pharmaceutical forms, particularly for clinical trial settings. This study proposes a liquid-filled capsule formulation designed to provide accurate dosing while protecting D-LSD from photodegradation. Methods: To support formulation development and ensure its suitability as an investigational medicinal product, a multi-tiered analytical strategy was employed. This included liquid chromatography coupled with ion mobility spectrometry and mass spectrometry (LC-IM-MS), along with quantum chemical calculations (density functional theory (DFT) and time dependent-DFT (TD-DFT)), to ensure robust and orthogonal structural characterization of degradation products. Results: Photostress studies demonstrated that while D-LSD in solution rapidly degrades into photoisomers and photooxidative byproducts, the capsule formulation markedly mitigates these transformations under ICH-compliant conditions. Conclusions: These findings highlight the essential role of orthogonal stability profiling in guiding formulation development and demonstrate that this approach may offer a viable, photostable platform for future clinical investigation of D-LSD in the treatment of AUD.<\/jats:p>","DOI":"10.3390\/pharmaceutics17060767","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T06:11:49Z","timestamp":1749622309000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stability-Guided Formulation of a Light-Sensitive D-LSD Capsule for Clinical Investigation"],"prefix":"10.3390","volume":"17","author":[{"given":"Bernard","family":"Do","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Institut des Sciences Mol\u00e9culaires d\u2019Orsay, CNRS, Universit\u00e9 Paris Saclay, 91400 Orsay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Mallet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Est Cr\u00e9teil, DMU IMPACT, D\u00e9partement M\u00e9dical-Universitaire de Psychiatrie et d\u2019Addictologie, H\u00f4pitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-H\u00f4pitaux de Paris, 94000 Cr\u00e9teil, France"},{"name":"Sorbonne Universit\u00e9, Institut du Cerveau-Paris Brain Institute\u2013ICM, Inserm, CNRS, 75013 Paris, France"},{"name":"Department of Mental Health and Psychiatry, Global Health Institute, University of Geneva, 12011 Geneva, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9594-2516","authenticated-orcid":false,"given":"Maxime","family":"Annereau","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Gustave Roussy Cancer Campus, 94805 Villejuif, France"},{"name":"Institut des Sciences Mol\u00e9culaires d\u2019Orsay, CNRS, Universit\u00e9 Paris Saclay, 91400 Orsay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Libong","sequence":"additional","affiliation":[{"name":"Lip(Sys)2\u2014Chimie Analytique Pharmaceutique, Universit\u00e9 Paris-Saclay, 91400 Orsay, France"},{"name":"UMS-IPSIT SAMM Facility, Universit\u00e9 Paris-Saclay, Inserm, CNRS, Ing\u00e9nierie et Plateformes au Service de l\u2019Innovation Th\u00e9rapeutique, 91400 Orsay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-0050","authenticated-orcid":false,"given":"Audrey","family":"Solgadi","sequence":"additional","affiliation":[{"name":"UMS-IPSIT SAMM Facility, Universit\u00e9 Paris-Saclay, Inserm, CNRS, Ing\u00e9nierie et Plateformes au Service de l\u2019Innovation Th\u00e9rapeutique, 91400 Orsay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-3727","authenticated-orcid":false,"given":"Florence","family":"Vorspan","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM UMRS 1144 Optimisation Th\u00e9rapeutique en Neuropharmacologie, 75006 Paris, France"},{"name":"APHP, GHU NORD, H\u00f4pital Fernand Widal, D\u00e9partement de Psychiatrie et de M\u00e9decine Addictologique, 75010 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Henri Mondor Hospital, AP-HP, 94000 Cr\u00e9teil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-3695","authenticated-orcid":false,"given":"Philippe-Henri","family":"Secretan","sequence":"additional","affiliation":[{"name":"Mat\u00e9riaux et Sant\u00e9, Universit\u00e9 Paris-Saclay, 91400 Orsay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s40265-021-01670-3","article-title":"Novel Agents for the Pharmacological Treatment of Alcohol Use Disorder","volume":"82","author":"Burnette","year":"2022","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.psychres.2019.05.038","article-title":"Alcohol Use Disorder Relapse Factors: A Systematic Review","volume":"278","author":"Sliedrecht","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alper, K., Dong, B., Shah, R., Sershen, H., and Vinod, K.Y. 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